Rheumatic fever and rheumatic heart disease are conditions that can occur after a streptococcal throat infection. Rheumatic fever is an inflammatory disease that affects the heart, joints, skin, and blood vessels. It is characterized by lesions called Aschoff bodies and rheumatic granulomas. Long term, it can lead to rheumatic heart disease where the heart valves are damaged. The disease process involves an immune response to streptococcal antigens that causes inflammation and tissue damage. Symptoms vary by the organs involved but can include fever, arthritis, heart valve abnormalities, and skin rashes.

1. Rheumatic Fever & Rheumatic
Heart Disease
Akshai George Paul

2. •Rheumatic fever (RF) is an acute, immunologically
mediated, multisystem inflammatory disease that occurs a
few weeks following an episode of group A streptococcal
pharyngitis.
•Major involvement of systemic connective tissue, it often
violate connective tissue of heart, joint, skin, and
subcutaneous and vascular connective tissue. Key
pathologic features is Rheumatic Granuloma.
•It occurs in children in age 5 to 15 years, 20% -adults
•The clinical course of rheumatic fever involves a
childhood infection with complications in adulthood
(cardiac defect).
Rheumatic Fever

3. Etiology and pathogenesis
It is an immune response associated with
streptococcal infection, but it is not caused
by bacteria directly effects.

4. 1. There is a streptococcus infection history before
the onset of RF.
2. A variety of antibodies of the streptococcus and
its products can be detected in the onset phase.
serous "O" antibody in 95% patients is high, >
500 units.
3. Regional distribution consistent with area of
streptococcal infection.
4. Antibiotic prophylaxis treatment is effective.
The evidence related with group A β-hemolytic
streptococcus infection including:

5. The evidence which is not directly caused by
streptococcus infection including:
1. The disease is not appeared in infected at the
time, but in 2-3 weeks later, it is in line with
emergence period of the general immune
response.
• No evidence of direct invasion of organ by
streptococcus.
• Streptococcus has never been found in the RF
patient's blood .
• Not purulent inflammation, but the fibrinoid
necrosis.

6. Antigen and antibody cross-reactivity:
The antigens of streptococcus may stimulate
the immunological cross-reactivity in
patients.

7. M antibody+Vascular
smooth muscle
C antibody+Cardiovascular
connective tissue
Pathogenesis
Antigen antibody complex
Local deposition
alexin platelet
activation of
coagulation
system Embolism,
bleeding
Neutrophil infiltration
Release of lysosomal enzymes(Neutral, acid hydrolases, elastase,
collagenase and so on
Blood vessel, tissue injury

8. Basic pathological changes
1. Exudative and degenerative phase
2. The proliferative phase (Granulomatous period)
3. Scar phase (healed phaseFibrosis phaseHardening
phase)

9. Exudative and degenerative phase
It is characterized by serofibrinous exudate, with deposits of
immune precipitate on collagen fibers that lead to fibrinoid
necrosis. About 1 months.

10. The proliferative phase (Granulomatous period)
Aschoff Body:
Structure:
center： fibrinoid necrosis
around the center：Anitschkow cells , lymphocytes,
occasional plasma cells
Distribution:
Myocardial interstitial, subendocardial and subcutaneous
connective tissue. Epicardial, joints and blood vessels is
rare.
pathognomonic for RF

11. Anitschkow cells:
These distinctive cells have abundant cytoplasm
and central round-to-ovoid nuclei in which the
chromatin is disposed in a central, slender, wavy
ribbon (hence the designation "caterpillar cells“--
cross section named Owl 's eye cells).
Some of the larger macrophages become
multinucleated to form Aschoff cells(inflammatory
giant cells).

14. The myocardial interstitium has a circumscribed collection of
mononuclear inflammatory cells, including some large histiocytes
with prominent nucleoli and a prominent binuclear histiocyte, and
central necrosis

16. Owl 's eye cells
Aschoff cells

17. Scar phase
Emergence of fibroblasts and collagen
production, formation of small spindle scar, 2-3
months or so.
The above three stages repeated attacks, the
old and new lesions coexist.
The whole course about 4-6 months.

18. RF involves various organs
Rheumatic heart disease
Rheumatic arthritis
Rheumatic arteritis
Rheumatic disease of skin
Rheumatic disease of brain

19. Rheumatic heart disease
Divided into rheumatic endocarditis,
rheumatic myocarditis and rheumatic
pericarditis, often for rheumatic
pancarditis.
60% to 80% children associated with
pancarditis。

20. Key morphologic
features of acute
rheumatic heart
disease.

21. rheumatic endocarditis
Lesions were most often involved: mitral valve
Secondly: both mitral and aortic valve
The most important lesions caused by rheumatism,
valvular deformity and dysfunction

22. Pathological changes:
early stage: serous endocarditis , valve swelling,translucent
Microscopically: valve become loose due to serous
exudate , accompanied by macrophages entering and
fibrinoid necrosis of collagen fiber.
Concomitant involvement of the endocardium and the left-
sided valves by inflammatory foci typically results the
small (diameter 1- to 2-mm) vegetations .
Vegetations: White thrombus consist of platelet and
cellulose.

23. Acute rheumatic endocarditis: small (diameter 1- to 2-mm)
vegetations along the mitral valve margin, insufficient to cause
valvular deformation.

24. Small vegetations (verruca) are visible along the line
of closure of the mitral valve leaflet (arrows).

25. Advanced: vegetations organization, recurrent organization cause
chronic heart valve disease ( valvular stenosis and / or valvular
insufficiency )

26. Mitral stenosis with diffuse fibrous thickening and distortion of
the valve leaflets, commissural fusion (arrows), and thickening
and shortening of the chordae tendineae.

27. rheumatic myocarditis
location:Myocardial interstitial
connective tissue
pathological changes: Rheumatic Granuloma

28. Perivascular Rheumatic Granuloma formation. Children often
occurred to diffuse myocardial interstitial edema, inflammatory
cell infiltration, congestive heart failure. Late effects myocardial
contractile force.

29. A serous or serous fibrinous inflammation. Can
form a pericardial effusion, trichocardia
and constrictive pericarditis.
rheumatic pericarditis

30. Serous pericarditis Fibrinous pericarditis

31. pericardial
effusion
Can lead to heart sound
far, around the heart
boundary expanding,
serious cardiac X-ray
showed a flask

32. Adhesive pericardit is in
cardiac surface of patients.
From the epicardial surface
to the pericardial sac visible
fibrinous exudate, which is
typical for a fibrinous
pericarditis.

33. trichocardia
Can lead to
precordial pain,
pericardial friction
sound, serious
cause constrictive
pericarditis,
influence on
cardiac function.

34.  Rheumatoid arthritis
 predilection age: Adults
 predilection site: involving the large joints, most
commonly in the knee and ankle joint, followed
by the shoulder, wrist, elbow and other joints
 Lesion characteristics: migratory polyarthritis.
Local serous exudate, appear red, swelling, heat,
pain and dysfunction. As the heals , serous
exudate is absorbed, generally no sequela.
 Microscopic lesions mainly for serous
inflammation.
 lick the knee but bite the heart.

35. Involving the coronary arteries, renal artery, brain
artery etc, small arteries see more.
Vascular wall connective tissue myxoid degeneration
and fibrinoid necrosis. There can see Rheumatic
Granuloma, and later wall narrow even block, with
thrombosis.
Rheumatoid coronary artery inflammation.
rheumatic arteritis

36. Mainly in acute period
1 subcutaneous nodules ( hyperplasia ):
2 The annular erythema (exudative lesions) :
Appear on the extremities and the trunk skin.
1-2 days. Hyperemia, edema changes of the
superficial layer of dermis. (pathognomonic )
Rheumatic disease of skin

37. annular erythema

39. Mainly involving the cerebral cortex, basal
ganglia, thalamus and cerebellum cortex.
Lesions to rheumatic arteritis and
subcortical encephalitis.
In 5-12 years old children, girls see more.
Rheumatic disease of brain

40. Infective endocarditis, one of the most serious of all
infections, is characterized by colonization or
invasion of the heart valves or the mural
endocardium by a microbe, leading to the formation
of bulky, friable vegetations composed of thrombotic
debris and organisms, often associated with
destruction of the underlying cardiac tissues.
Infective endocarditis
(IE)

41. Traditionally, IE has been classified on
clinical grounds into acute and subacute forms.
1. Acute IE
2. Subacute IE

42. 1Acute IE :The strong pathogenic pyogenic bacteria
（carbuncle, puerperal fever, osteomyelitis ）---
resistance down---bacteria into the blood---sepsis---
normal endocardium ---invasion of mitral valve,
aortic valve---acute septic endocarditis---bacterial
vegetations
2Subacute IE: Streptococcus viridans (localized
infection focus in vivo or iatrogenic infection)----
bacteria into the blood---the mitral valve or/and
aortic valve with original lesions （ 80%,
congenital heart disease, RHD or valve repair)--
Subacute IE--bacterial vegetations

43. Pathological change
In both the subacute and acute forms of the disease,
friable, bulky, and potentially destructive vegetations
containing fibrin, inflammatory cells, and bacteria or
other organisms are present on the heart valves.

44. vegetations ( microscopic ): cellulose + platelet +inflammatory
cell + bacteria group

45. In the aortic opening a larger, irregular red vegetations, this
mostly by Staphylococcus aureus infection.

46. Acute IE :Caused the distant organ septic infarction and abscess.
Valve rupture, perforation, rupture of chordae tendineae, leading
to chronic valvular heart disease. 50% died in days or weeks.

47. Subacute IE

48. End and complications：
1.Fever: it is the most consistent sign of IE. However, with
subacute disease, particularly in the elderly, fever
may be slight or absent, and the only manifestations
are sometimes nonspecific fatigue, loss of weight, and
a flulike syndrome. In contrast, acute endocarditis
has a stormy onset with rapidly developing fever,
chills, weakness, and lassitude.
2.Arterial embolization ( 20%-40% ): embolism of
brain ,heart, kidney, spleen, mesenteric, limbs and
pulmonary.

49. 3.Chronic valvular disease
4.non-specific symptoms:
Splenomegaly (15%-50% )
Anemia
Clubbing finger / toe
5. Peripheral symptoms

50. splinter or subungual
hemorrhages
Osler nodes
Janeway lesions
Roth spots
Peripheral symptoms
Peripheral symptoms: Micro vasculitis or micro
thrombus

51. splinter or subungual Hemorrhages:petechiae, red, linear, or
flame-shaped streaks in the nail bed of the digits

52. Osler nodes :
retinal hemorrhages

53. Janeway lesions: are small erythematous or hemorrhagic,
macular, nontender lesions on the palms and soles and are the
consequence of septic embolic events.

54. Osler nodes: are small, tender subcutaneous nodules that
develop in the pulp of the digits or occasionally more
proximally in the fingers and persist for hours to several days.

55. 杵状指/趾

56. Subacute IE Acute IE
bacterial
virulence
weak strong
valve Have lesions normal
Dry, crisp A larger, soft
vegetation Bacteria are less, little
or no necrosis
 Many bacteria,
much necrosis
final result the vast majority of
people heal
50% died in days or
weeks.
Bacteria
into the
blood
ichorrhemia Sepsis
embolism Non-infectious
infarction
Multiple embolic
microabscesses

57. rheumatic
endocarditis
Subacute IE
Etiology immunologically
mediated
bacterial infection
grossly White, small, compact
vegetations
gray red, large, loose
vegetations, fall off
easily
microscopically white thrombus White thrombus with
necrosis, colony etc.
clinical feature Valvular Disease Valvular heart disease,
thromboembolism,
infarction, Septicemia
connection SIE often occurs on
the basis of RE